<i>Citrobacter rodentium</i>, a Gut Pathogen: The Yin and the Yang of Its Pathophysiology, Immunity and Clinical Manifestation in Mice

Abstract

Pathogenic strains of E. coli including enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), enterotoxigenic E. coli (ETEC) are principle causes for diarrhoea in many parts of the globe. Citrobacter rodentium (C. rodentium), a gram negative bacterium, is a murine pathogen that also utilizes type III secretion system and similar virulence factors to EPEC and EHEC and forms comparable attaching/effacing lesions in the intestines as EPEC and EHEC. The infection caused by C. rodentium in mice is usually self-limiting and results in only minor systemic effects with higher mortality in some susceptible mouse strains. All these characteristics have made the bacteria a commonly used model to study host immune responses to pathogenic E. coli infection. In this review, we focus on the impact of virulence factors of the pathogen; different immune components involved in the immune response and summarize their role during C. rodentium infection.

Efficacy of EHEC gold nanoparticle vaccines evaluated with the Shiga toxin-producing Citrobacter rodentium mouse model

“…The murine pathogen C. rodentium is often considered the mouse counterpart of EHEC because it leads to the development of the hallmark A/E lesions in mice and encodes a conserved LEE genomic pathogenicity island essential for virulence ( 22 , 23 ). While this pathogen can be used as a model for EHEC infection in mice because it also leads to outward disease symptoms like diarrhea, weight loss, and even death, its utility is still limited due to its varying and inconsistent severity in different mouse strains ( 39 – 41 ).…”

“…For this reason, the pathogen Citrobacter rodentium has been employed as a model for infection. This pathogen is the causative agent of transmissible murine colonic hyperplasia and leads to disease manifestations such as weight loss, diarrhea, and even death in severe cases ( 22 ). Like EHEC, it also encodes for a conserved LEE T3SS and can form A/E lesions on IECs ( 23 ).…”

Further Evaluation of Enterohemorrhagic Escherichia coli Gold Nanoparticle Vaccines Utilizing Citrobacter rodentium as the Model Organism

“…Another model that has been extensively used to study EHEC pathogenesis is C. rodentium, the causative agent of transmissible murine hyperplasia, because it also encodes for the LEE and triggers A/E lesions in the large intestine [22,40]. Infection of mice with (A) Feces, ceca, and large intestines (LIs) were collected from AuNP-protein-immunized or adjuvantonly-treated mice infected with either 10 9 or 10 6 CFU of DBS771 at 14 dpi, homogenized, and plated.…”

“…Another model that has been extensively used to study EHEC pathogenesis is C. rodentium, the causative agent of transmissible murine hyperplasia, because it also encodes for the LEE and triggers A/E lesions in the large intestine [22,40]. Infection of mice with wild-type C. rodentium can result in signs such as diarrhea, weight loss, intestinal inflammatory damage, and even death; however, the usefulness of this model in evaluating EHEC vaccines is still limited because disease severity is inconsistent among mouse strains and the pathogen does not naturally produce Stx [41,42].…”